Haarstad H, Jacobsen A B, Schjølseth S A, Risberg T, Fosså S D
Department of Oncology, Regional Hospital Trondheim, Norway.
Ann Oncol. 1994 Mar;5(3):245-8. doi: 10.1093/oxfordjournals.annonc.a058801.
Due to the possibility of a synergistic effect between Interferon (IFN-alpha) and 5-fluorouracil (5-FU), a phase II trial was conducted in metastatic renal cell carcinoma (MRCC) combining recombinant IFN-alpha, 5-FU and prednisone. Prednisone has been shown to decrease IFN-alpha-related toxicity without reducing the response rate.
Thirty-one patients with measurable MRCC were entered into the trial; 16 of them had lung metastases only. In 26 patients (nos. 6-31) the following dose schedule was applied during an 8-week treatment cycle: IFN-alpha (Roferon, Roche, Basel, Switzerland): 12 x 10(6)U s.c. 3 times weekly; Days 1-5: 5-FU: 600 mg/m2/day continuous i.v. infusion; Weeks 3-8: 5-FU 600 mg/m2 x 1 weekly (bolus i.v.); prednisone: 10 mg x 2 per os daily for 2 weeks, and thereafter 5 mg x 2. In the first 5 patients higher doses of 5-FU led to unacceptable toxicity and subsequent dose alteration of the trial schedule. All 31 patients were evaluable for response. Seventy treatment cycles were given.
One complete and 6 partial responses were observed (response rate: 23%, 95% CI: 10%-41%), with a median response duration of 11 months. Except in one patient, hematological toxicity was confined to grades I and II. Eight patients developed grade III oral mucositis. Adverse cardiac events were observed in 3 patients. Dose modifications of 5-FU were necessary in 16 cycles. The IFN-alpha doses were transiently reduced during 8 cycles.
The assessed combination of IFN-alpha, 5-FU and prednisone is moderately active in MRCC, with response rates similar to those seen in patients on IFN-alpha monotherapy. The latter treatment approach seems preferable, as 5-FU-related toxicity (mucositis, cardiac toxicity) is averted.
由于干扰素（IFN-α）与5-氟尿嘧啶（5-FU）之间可能存在协同作用，因此开展了一项针对转移性肾细胞癌（MRCC）的II期试验，将重组IFN-α、5-FU与泼尼松联合使用。已证实泼尼松可降低IFN-α相关毒性，且不降低缓解率。
31例可测量的MRCC患者进入该试验；其中16例仅发生肺转移。在26例患者（第6 - 31号）中，在8周的治疗周期内采用以下给药方案：IFN-α（罗扰素，罗氏公司，瑞士巴塞尔）：12×10⁶U皮下注射，每周3次；第1 - 5天：5-FU：600mg/m²/天持续静脉输注；第3 - 8周：5-FU 600mg/m²每周1次（静脉推注）；泼尼松：第1周每日口服10mg×2次，共2周，之后每日口服5mg×2次。在前5例患者中，较高剂量的5-FU导致了无法接受的毒性，随后对试验方案进行了剂量调整。所有31例患者均可评估疗效。共进行了70个治疗周期。
观察到1例完全缓解和6例部分缓解（缓解率：23%，95%置信区间：10% - 41%），中位缓解持续时间为11个月。除1例患者外，血液学毒性仅限于I级和II级。8例患者出现III级口腔黏膜炎。3例患者出现不良心脏事件。16个周期需要对5-FU进行剂量调整。8个周期内IFN-α剂量曾短暂降低。
所评估的IFN-α、5-FU和泼尼松联合方案在MRCC中有中度活性，缓解率与IFN-α单药治疗的患者相似。后一种治疗方法似乎更可取，因为可避免5-FU相关毒性（黏膜炎、心脏毒性）。
